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Previous work in animal models suggests that inhalational anesthetic agents may accelerate Alzheimer's disease pathogenesis, but it is unclear to what extent this may happen in humans. Here, the investigators propose to measure Alzheimer's disease-related neural markers in the cerebrospinal fluid (CSF) of patients exposed to anesthesia while undergoing neurosurgical procedures that require lumbar drain placement. Patients will be randomized to either receive inhalation anesthesia with isoflurane or intravenous anesthesia with propofol.
CSF and blood samples will each be collected at the induction of anesthesia, and then again ten and twenty-four hours later. CSF samples will be assayed for amyloid beta, tau, and other Alzheimer's disease-associated markers; blood samples will be assayed for serum inflammatory markers and used for genotyping studies. These studies should clarify the effect of common anesthetic agents on Alzheimer's disease related neural markers.
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| Propofol based intravenous anesthesia | Active Comparator | patients will receive propofol based intravenous anesthesia |
|
| Isoflurane Based Inhaled Anesthesia | Experimental | patients will receive isoflurane based inhaled anesthesia |
|
| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| Propofol | Drug | patients randomized to the propofol arm of the study will receive general anesthesia with propofol |
|
| Measure | Description | Time Frame |
|---|---|---|
| Ratio of cerebrospinal fluid tau to amyloid beta | twenty four hours after the induction of anesthesia |
| Measure | Description | Time Frame |
|---|---|---|
| the relationship between anesthetic exposure and CSF biomarker changes | up to 24 hrs after induction of anesthesia | |
| the relationship between anesthetic exposure and CSF biomarker changes, and demographics (age, gender, and race) | up to 24 hrs after induction of anesthesia |
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Inclusion Criteria:
Exclusion Criteria:
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| Name | Affiliation | Role |
|---|---|---|
| Miles Berger, MD, PhD | Duke University Medical Center, Department of Anesthesiology | Principal Investigator |
| Michael L James, MD | Duke University Medical Center, Department of Anesthesiology | Principal Investigator |
| David McDonagh, MD | Duke University Medical Center, Department of Anesthesiology | Principal Investigator |
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| Duke University Medical Center | Durham | North Carolina | 27709 | United States |
| PubMed Identifier | Type | Citation | Retractions |
|---|---|---|---|
| 29181002 | Derived | Berger M, Ponnusamy V, Greene N, Cooter M, Nadler JW, Friedman A, McDonagh DL, Laskowitz DT, Newman MF, Shaw LM, Warner DS, Mathew JP, James ML; MAD-PIA Investigators. The Effect of Propofol vs. Isoflurane Anesthesia on Postoperative Changes in Cerebrospinal Fluid Cytokine Levels: Results from a Randomized Trial. Front Immunol. 2017 Nov 13;8:1528. doi: 10.3389/fimmu.2017.01528. eCollection 2017. | |
| 27079717 |
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| ID | Term |
|---|---|
| D000544 | Alzheimer Disease |
| D060825 | Cognitive Dysfunction |
| ID | Term |
|---|---|
| D003704 | Dementia |
| D001927 | Brain Diseases |
| D002493 | Central Nervous System Diseases |
| D009422 | Nervous System Diseases |
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| ID | Term |
|---|---|
| D015742 | Propofol |
| D007530 | Isoflurane |
| ID | Term |
|---|---|
| D010636 | Phenols |
| D001555 | Benzene Derivatives |
| D006841 | Hydrocarbons, Aromatic |
| D006844 | Hydrocarbons, Cyclic |
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| Isoflurane | Drug | patients randomized to the isoflurane arm of the study will receive general anesthesia with isoflurane |
|
| the relationship between CSF biomarker changes and serum markers of metabolic and/or inflammatory status | up to 24 hrs after induction of anesthesia |
| the relationship between anesthetic exposure and biomarker changes and serum markers of metabolic and/or inflammatory status | up to 24 hrs after induction of anesthesia |
| the relationship between anesthetic exposure and biomarker changes and neuroimaging results obtained as dictated by routine standard of care | up to 24 hours after induction of anesthesia |
| the relationship between anesthetic exposure and biomarker changes and depth of anesthesia, based on average BIS (bispectral index) monitoring signal | up to 24 hours after induction of anesthesia |
| the relationship between anesthetic exposure and biomarker changes and the time of day that surgery is performed | up to 24 hours after induction of anesthesia |
| the relationship between anesthetic exposure and biomarker changes with genetic polymorphisms in ApoE (apolipoprotein E) and other genes related to inflammation, metabolism, brain function and/or Alzheimer's disease | up to 24 hours after induction of anesthesia |
| Derived |
| Berger M, Nadler JW, Friedman A, McDonagh DL, Bennett ER, Cooter M, Qi W, Laskowitz DT, Ponnusamy V, Newman MF, Shaw LM, Warner DS, Mathew JP, James ML; MAD-PIA trial team. The Effect of Propofol Versus Isoflurane Anesthesia on Human Cerebrospinal Fluid Markers of Alzheimer's Disease: Results of a Randomized Trial. J Alzheimers Dis. 2016 Apr 15;52(4):1299-310. doi: 10.3233/JAD-151190. |
| D024801 |
| Tauopathies |
| D019636 | Neurodegenerative Diseases |
| D019965 | Neurocognitive Disorders |
| D001523 | Mental Disorders |
| D003072 | Cognition Disorders |
| D006838 |
| Hydrocarbons |
| D009930 | Organic Chemicals |
| D008738 | Methyl Ethers |
| D004987 | Ethers |